The investigation of the major determinants of monoamine synthesis and turnover in vivo is of intense scientific interest because monoamine levels in the central nervous system (CNS) play critical roles in neuropsychiatric, neuroendocrine and cardiovascular diseases. Tyrosine hydroxylase is known to be the rate-limiting enzymatic step in the synthesis of dopamine and norepinephrine. Current evidence suggests that in vivo rate of synthesis depends primarily on dopamine concentration (due to end-product inhibition) and pteridine cofactor levels. Thus, pteridine levels in cerebrospinal fluid (CSF) are of interest. This study was undertaken to detect and monitor CSF pteridine cofactor activity using a phenylalanine hydroxylase assay (Bullard, W.P. et al., Dynamics and disposition of reduced pterins in rat brain, JPET, in press). Preliminary results show that cofactor activity is detectable in CSF of patients with a variety of neuropsychiatric disorders. Cofactor activity is stable in CSF stored at -70 degrees C in liquid N2 for a period of several days. The data suggest that patients with neurological disorders which include parkinsonism, and multiple sclerosis and Huntington's chorea, have lower mean cofactor activity in CSF than patients with schizophrenia and affective disorders.